The origin and meiotic behavior of Robertsonian translocations

Abstract

Robertsonian translocations, whole arm chromosomal exchanges between acrocentric chromosomes, are the most common human structural chromosomal abnormality (1/1000 individuals). While these translocations have been thoroughly investigated in insects and some mammals, relatively little is known about the structure and formation of Robertsonian translocations in humans. In addition, the effect of this chromosomal aberration on the frequency and location of recombination during meiosis is poorly understood. Fluorescence in situ hybridization with five biotin-labeled probes was used to characterize 30 different Robertsonian translocations. Of 8 de novo homologous translocations, only one was interpreted as dicentric, while 19 of 22 nonhomologous Robertsonian translocations were dicentric. Two of 26 translocations studied using the beta satellite probe showed a positive signal, while ribosomal DNA was undetectable in ten cases studied. This analysis demonstrated that a majority of the breakpoints could be localized distal to the centromere and just proximal to the beta satellite and NOR regions of the short arm. The availability of appropriate DNA probes for restriction fragment length polymorphisms (RFLPs) permits the study of the origin of Robertsonian translocations, as well as the analysis of meiotic recombination frequencies for both the translocation chromosomes and their normal homologs. For the present study, 15 Robertsonian translocation families were studied using eight RFLPs from chromosome No. 21. Five families with de novo Robertsonian translocations were studied to determine the parental origin of the translocation. Two t(21;21) were found to originate from the father, while two out of three of the t(14;21) originated during maternal meioses (the last case was not informative). These results support previous findings of preferential formation of t(14;21) during maternal meiosis (20/21 of cases reported). Numerous studies in insects and in a few mammals have shown that chromosomal rearrangements, such as translocations, may cause intra- and interchromosomal effects. Studies in five familial Robertsonian translocations (one t(13;21) and four t(14;21)) revealed an increased frequency of crossing over in the long arm of chromosome 21, as well as a more proximal placement of the crossover events, in relation to the centromere. This finding demonstrates an intrachromosomal effect of the Robertsonian translocation on chromosomes 21 involved in the rearrangements. In contrast, no interchromosomal effect was revealed for chromosome 21 in five additional non-21 Robertsonian translocations (three t (13;14) and two t(14;22)). In these families, there was no significant alteration in either the frequency or location of crossing over.